Anti-aging and skin tone lightening compositions and methods for same

ABSTRACT

Embodiments of the invention are directed to compositions containing cannabinoid, cannabidiol, or cannabidiol analog for lightening or whitening skin, and methods for lightening skin tone or whitening skin by administering compositions containing cannabinoid, cannabidiol, or cannabidiol analog to the skin.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. application Ser. No.16/246,823 entitled “Anti-Aging and Skin Tone Lightening Compositionsand Methods for Same,” filed Jan. 14, 2019, which claims priority fromU.S. Provisional Application No. 62/617,215 entitled “Compositions ForLightening Skin Tone And Methods For Same,” filed Jan. 13, 2018 and U.S.Provisional Application No. 62/702,973 entitled “Anti-aging CompositionsAnd Compositions For Lightening Skin Tone And Methods For Same,” filedJul. 25, 2018 the entireties of which are hereby incorporated byreference in their entireties.

GOVERNMENT INTERESTS

Not applicable

PARTIES TO A JOINT RESEARCH AGREEMENT

Not applicable

INCORPORATION OF MATERIAL ON COMPACT DISC

Not applicable

BACKGROUND

Cannabinoids are a class of diverse chemical compounds that act oncannabinoid receptors on cells that modulate physiological responses inthe brain, peripheral nervous and immune systems. The nativeendocannabinoid ligands (produced naturally in the body by humans andanimals), the phytocannabinoids (found in cannabis and some otherplants), and synthetic cannabinoids (manufactured chemically) bind toreceptors throughout the body and control downstream signaltransduction. One example of a cannabinoid is Cannabidiol (CBD), whichis a major substituent in hemp and hemp extracts. It may have multiplepotential applications such as for the treatment of epilepsy and othermotor disorders, inflammation, mood and anxiety disorders, sleepdysfunction and eating disorders. CBD is also considered a promisingantineoplastic agent on the basis of its in vitro and in vivo activityagainst tumor cells.

The endocannabinoid system (ECS) regulates many physiological processesinvolved in relaxation, eating, sleeping, certain inflammatory responsesand even cognitive function. There are two types of cannabinoidreceptors found throughout the body (CB1 and CB2), but they are mostabundant in the brain and immune system respectively. In fact, the CB1receptor is the most densely populated G-coupled protein receptor in thehuman brain. New evidence indicates that a cannabinoid-like ligands acton wide variety of biological targets, such as the transient receptorpotential cation channel, nuclear receptors and other orphaned G-coupledprotein receptors (i.e., TRPV1, PPAR, GPR18 and GPR55), and represents afascinating area to develop new therapeutic targets.

SUMMARY OF THE INVENTION

Various embodiments are directed to topical formulations containing acannabinoid, cannabidiol, or cannabidiol analog, a carrier, excipient,diluent, reagent, or combinations thereof, and an additive. Otherembodiments include methods for lightening skin tone including topicallyadministering a composition containing a cannabinoid, cannabidiol,cannabidiol analog, or combinations thereof, where lighteningencompasses lightening color of skin, reducing production of melanin,diminishing the amount of melanin in skin, reducing visible redness, orcombinations thereof.

Some embodiments are directed to topical anti-aging formulations. Theanti-aging formulations may include cannabidiols, cannabidiol isomers,cannabidiol analogs, or combinations thereof and a carrier, excipient,diluent, reagent, or combinations thereof. And in some embodiments, suchformulations may further include one or more anti-oxidants,anti-wrinkling agents, anti-inflammatory agents, emollients, proactants,conditioning agents, and combinations thereof. Such formulations mayinterrupt or prevent the production of tyrosinase and melanin and may aprovide a reduction in fine lines and wrinkles as well as firming andlifting of the skin to reduce notable sagging.

DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

For a fuller understanding of the nature and advantages of the presentinvention, reference should be made to the following detaileddescription taken in connection with the accompanying drawings, inwhich:

FIG. 1A-c shows the effects of skin exposed to cannabidiol containingfluids that exhibits significantly lighter skin tone, reductionpigmentation, and reduction of observable blemishes, such as, freckles.

FIG. 1A shows right (treated) and left (control) hands of a subjectprior to treatment with a CBDA skin lightening composition.

FIG. 1B shows right (treated) and left (control) hands of the subject ofFIG. 1A after 14 days of twice daily treatment with a CBDA skinlightening composition.

FIG. 1C shows right (treated) and left (control) hands of the subject ofFIG. 1A after 35 days of twice daily treatment with a CBDA skinlightening composition.

FIG. 2 shows the hand of a subject after treatment with a CBDA skinlightening composition. Skin lightening and reduction in freckles on theback of the hand as compared to the forearm are seen.

DETAILED DESCRIPTION

Where a range of values is provided, it is intended that eachintervening value between the upper and lower limit of that range andany other stated or intervening value in that stated range isencompassed within the disclosure. For example, if a range of 1 um to 8um is stated, 2 um, 3 um, 4 um, 5 um, 6 um, and 7 um are also intendedto be explicitly disclosed, as well as the range of values greater thanor equal to 1 um and the range of values less than or equal to 8 um.

All percentages, parts and ratios are based upon the total weight of thetopical compositions and all measurements made are at about 25° C.,unless otherwise specified.

The singular forms “a,” “an,” and “the” include plural referents unlessthe context clearly dictates otherwise. Thus, for example, reference toa “polymer” includes a single polymer as well as two or more of the sameor different polymers; reference to an “excipient” includes a singleexcipient as well as two or more of the same or different excipients,and the like.

The word “about” when immediately preceding a numerical value means arange of plus or minus 10% of that value, e.g., “about 50” means 45 to55, “about 25,000” means 22,500 to 27,500, etc., unless the context ofthe disclosure indicates otherwise, or is inconsistent with such aninterpretation. For example, in a list of numerical values such as“about 49, about 50, about 55, about 50” means a range extending to lessthan half the interval(s) between the preceding and subsequent values,e.g., more than 49.5 to less than 52.5. Furthermore, the phrases “lessthan about” a value or “greater than about” a value should be understoodin view of the definition of the term “about” provided herein.

The terms “administer,” “administering” or “administration” as usedherein refer to either directly administering a compound (also referredto as an agent of interest) or pharmaceutically acceptable salt of thecompound (agent of interest) or a composition to a subject.

The term “carrier” as used herein encompasses carriers, excipients, anddiluents, meaning a material, composition or vehicle, such as a liquidor solid filler, diluent, excipient, solvent or encapsulating materialinvolved in carrying or transporting a pharmaceutical, cosmetic or otheragent across a tissue layer such as the stratum corneum or stratumspinosum.

The transitional term “comprising,” which is synonymous with“including,” “containing,” or “characterized by,” is inclusive oropen-ended and does not exclude additional, unrecited elements or methodsteps. By contrast, the transitional phrase “consisting of” excludes anyelement, step, or ingredient not specified in the claim. Thetransitional phrase “consisting essentially of” limits the scope of aclaim to the specified materials or steps “and those that do notmaterially affect the basic and novel characteristic(s)” of the claimedinvention. In embodiments or claims where the term comprising is used asthe transition phrase, such embodiments can also be envisioned withreplacement of the term “comprising” with the terms “consisting of” or“consisting essentially of.”

The phrase “pharmaceutically acceptable” or “cosmetically acceptable” isemployed herein to refer to those agents of interest/compounds, salts,compositions, dosage forms, etc, which are—within the scope of soundmedical judgment suitable for use in contact with the tissues of humanbeings and/or other mammals without excessive toxicity, irritation,allergic response, or other problem or complication, commensurate with areasonable benefit/risk ratio. In some aspects, pharmaceuticallyacceptable means approved by a regulatory agency of the federal or astate government, or listed in the U.S. Pharmacopeia or other generallyrecognized pharmacopeia for use in mammals (e.g, animals), and moreparticularly, in humans.

The term “salts” as used herein embraces pharmaceutically acceptablesalts commonly used to form alkali metal salts of free acids and to formaddition salts of free bases. The nature of the salt is not critical,provided that it is pharmaceutically acceptable. The term “salts” alsoincludes solvates of addition salts, such as hydrates, as well aspolymorphs of addition salts. Suitable pharmaceutically acceptable acidaddition salts can be prepared from an inorganic acid or from an organicacid. Non-limiting examples of such inorganic acids are hydrochloric,hydrobromic, hydroiodic, nitric, carbonic, sulfuric, and phosphoricacid. Appropriate organic acids can be selected from aliphatic,cycloaliphatic, aromatic, arylaliphatic, and heterocyclyl containingcarboxylic acids and sulfonic acids, for example formic, acetic,propionic, succinic, glycolic, gluconic, lactic, malic, tartaric,citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic,glutamic, benzoic, anthranilic, mesylic, stearic, salicylic,p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic),methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic,toluenesulfonic, 2-hydroxyethanesulfonic, sulfanilic,cyclohexylaminosulfonic, algenic, hydroxybutyric, galactaric andgalacturonic acid.

The term “patient” and “subject are interchangeable and may be taken tomean any living organism which may be treated with compounds of thepresent invention. As such, the terms “patient” and “subject” mayinclude, but is not limited to, any non-human mammal, primate or human.In some embodiments, the “patient” or “subject is a mammal, such asmice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep,horses, primates, or humans. In some embodiments, the patient or subjectis an adult, child or infant. In some embodiments, the patient orsubject is a human.

The term “treating” is used herein, for instance, in reference tomethods of treating a skin disorder or a systemic condition, andgenerally includes the administration of a compound or composition whichreduces the frequency of, or delays the onset of, symptoms of a medicalcondition or enhance the texture, appearance, color, sensation, orhydration of the intended tissue treatment area of the tissue surface ina subject relative to a subject not receiving the compound orcomposition. This can include reversing, reducing, or arresting thesymptoms, clinical signs, and underlying pathology of a condition in amanner to improve or stabilize a subject's condition.

By hereby reserving the right to proviso out or exclude any individualmembers of any such group, including any sub-ranges or combinations ofsub-ranges within the group, that can be claimed according to a range orin any similar manner, less than the full measure of this disclosure canbe claimed for any reason. Further, by hereby reserving the right toproviso out or exclude any individual substituents, analogs, compounds,ligands, structures, or groups thereof, or any members of a claimedgroup, less than the full measure of this disclosure can be claimed forany reason. Throughout this disclosure, various patents, patentapplications and publications are referenced. The disclosures of thesepatents, patent applications and publications in their entireties areincorporated into this disclosure by reference in order to more fullydescribe the state of the art as known to those skilled therein as ofthe date of this disclosure. This disclosure will govern in the instancethat there is any inconsistency between the patents, patent applicationsand publications cited and this disclosure.

For convenience, certain terms employed in the specification, examplesand claims are collected here. Unless defined otherwise, all technicaland scientific terms used in this disclosure have the same meanings ascommonly understood by one of ordinary skill in the art to which thisdisclosure belongs.

Various embodiments are directed methods for lightening or whiteningskin by topically administering a composition containing cannabinoids toskin. Other embodiments include topical compositions containingcannabinoids for lightening or whitening skin. In some embodiments, theformulations may act as anti-aging formulations that produce a reductionin fine lines and wrinkles, while firming and lifting of the skinfollowing treatment. In some embodiments, the compositions of theinvention may promote collagen generation.

The cannabinoids of such embodiments include any of a broad class ofcompounds that are known to interact with cannabinoid receptors, andencompass endocannabinoids (produced naturally in the body by animals),the phytocannabinoids (found in cannabis and some other plants), andsynthetic cannabinoids (manufactured artificially). Example cannabinoidsinclude, but are not limited to, tetrahydropyran analogs, such as,19-tetrahydrocannabinol, 18-tetrahydrocannabinol,6,6,9-trimythel-3-pentyl-6H-dibenzo[b,d]pyran-1-ol,3-(1,1-dimethylheptyl)-6,6a7,8,10,10ahexahydro-1-1hydroxy-6,6-dimythel-9H-dibezo[b,d]pyran-9-ol,(−)-(3S,4S)-7-hydroxy-delta-6tetrahydrocannabinol-1,1-dimethylheptyl,(+)-(3S,4S)-7-hydroxy-A-6-tetrahydrocannabinol, andA8-tetrahydrocannabinol-11-oic acid, piperidine analogs, such as, ()-(6S,6R,9R,10aR)5,6,6,7,8,9,10,10a-octahydro-6-methyl-1-3-[(R)-1-methyl-4-phenylbutoxy)-1,9phenanthridinediol 1-acetate), aminoalkylindole analogs, such as,(R)-(+)-[2,3-dihydro-5-methyl-3(4-morpholinylmethyl)-pyrrolo[1,2,3,-de]-1,4-benzoxazin-6-yl)-1-naphthelenyl-methanone,open pyran-ring analogs, such as,2-[3-methyl-6-(1-methylethenyl-2-cyclohexen-1-yl]-5-pentyl-1,3benzendi-ol,and4-(1,1-dimethylheptyl)-2,3′-dihydroxy-6′-a-(3-hydroxypropyl)-1′,-2′,3′,4′,5′,6′hexahydrobiphenyl, lipophilic alkylamides, such as,dodeca-2E,4E,8Z,10E/Z-tetraenoic-acid isobutylamide, cannabinoidmimetics, salts, solvates, metabolites, and metabolic precursors ofthese compounds and combinations thereof. In some embodiments, thecannabinoids may be derived plants including hemp, Echinacea purpurea,Echinacea angustifolia, Acmella oleracea, Helichrysum umbraculigerum,Radula marginata, and combinations thereof and oils made from theseplants, and in other embodiments, the cannabinoids may be manufacturedor chemically synthesized.

The compositions of various embodiments can include any number ofcannabinoids in various concentrations; however, in certain embodiments,the cannabinoid may be cannabidiol(2-(6-isopropenyl-3-methyl-5-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol).Cannabidiol has 7 double bonds and 30 stereoisomers. Embodiments includecompositions containing each stereoisomer individually and compositionscontaining a combination of these stereoisomers. In particularembodiments, the compositions used in the methods of embodiments and thecompositions of embodiments may include high concentrations ofcannabidiol. For example, in some embodiments, cannabidiol may be about30 w/v % to about 100 w/v % of the cannabinoids in the composition, andin other embodiments cannabidiol may be about 50 w/v % to about 100 w/v%, about 75 w/v % to about 100 w/v %, about 80 w/v % to about 100 w/v %,about 90 w/v % to about 100 w/v % of the cannabinoids in thecomposition.

Cannabidiol can be obtained by cold-pressing industrial hemp with traceamounts of THC. Cannabidiol in this present invention is provided as anatural constituent of hemp oil.

In some embodiments, the cannabinoids in the composition may becannabidiol analogs. The term “cannabidiol analogs” refers tosynthetically produced compounds that are structurally similar, but notstructurally identical, to cannabidiol. Various cannabidiol analogs areknown in the art and embodiments encompass such cannabidiol analogs. Forexample, PCT Publication WO2017/132526 and U.S. Pat. No. 6,630,507,which are each hereby incorporated by reference in their entireties,describes various analogs of cannabidiol. In some embodiments, theanalogs of cannabidiol may be of general Formula I:

where R¹ is hydrogen, methyl, linear or branched C₂-C₁₀ alkyl, linear orbranched C₂-C₁₀ alkenyl, linear or branched C₂-C₁₀ substituted alkyl,linear or branched C₂-C₁₀ substituted alkenyl, R² and R³ are each,individually, hydrogen, methyl, linear or branched C₂-C₁₀ alkyl, linearor branched C₂-C₁₀ substituted alkyl, linear or branched C₂-C₁₀ alkenyl,linear or branched C₂-C₁₀ substituted alkenyl, linear or branched C₂-C₁₀acyl, linear or branched C₂-C₁₀ substituted acyl, an amine or aminoacid, amino acid ester, R⁴ is hydrogen, substituted or unsubstitutedalkyl, carboxyl, alkoxy, aryl, aryloxy, arylalkyl, halo or amino, and nmay an integer of 2 to 10 and the like and salts and solvates thereof.In some embodiments, R² and R³ may, independently, be a linear orbranched, substituted or unsubstituted C₂-C₁₀ acyl having a carboxylicacid terminus thereby producing a dicarboxylic acid, and salts thereof.Like cannabidiol, cannabidiol analogs can have various isomers.Embodiments include all isomers of the such cannabidiol analogs.

In some embodiments, cannabidiol analogs, such as those described abovemay be combined with cannabidiol, to produce a mixture of cannabidioland cannabidiol analogs. Thus, as used herein the term “cannabidiol”encompasses cannabidiol, cannabidiol analogs, and the various isomers ofcannabidiol and cannabidiol analogs.

The compositions of embodiments of the invention can include 100%cannabidiol, and oils, solvents, and emulsions containing cannabidiol.For example, in some embodiments, the compositions of the invention mayinclude cannabidiol derived from hempseed oil. Hempseed oil is generallymanufactured from varieties of Cannabis sativa that do not containsignificant amounts of tetrahydrocannabinol (THC), the psychoactiveelement of the cannabis plant. This manufacturing process typicallyincludes cleaning the seed to 99.99% before pressing the oil. Hempseedoil generally also contains omega-6 and omega-3 fatty acids. Forexample, about 30 35% of the weight of hempseed oil are essential fattyacids (EFAs), i.e., linoleic acid, omega-6 (LA, 55%), a-linolenic acid,omega-3 (ALA, 22%), y-linolenic acid, omega-6 (GLA, 1-4%), stearidonicacid, and omega-3 (SDA, 0-2%). Thus, the compositions of someembodiments may contain fatty acids such as omega-6 and omega-3 fattyacids.

The form of the topical formulations of the invention is not limited.Non-limiting examples of the form include an oil, lotion, a cream, asalve, a liniment, an ointment, a gel, a paste, a soap, a shampoo, and alip balm.

Oils include cannabidiol oil and various plant derived oils containingcannabidiol, such as, hempseed oil, Echinacea purpurea, Echinaceaangustifolia, Acmella oleracea, Helichrysum umbraculigerum, Radulamarginata, and the like. In some embodiments, cannabidiol isolated fromsuch plants or made synthetically may be formulated with an oil such as,for example, cottonseed oil, olive oil, grapeseed oil, tea tree oil,almond oil, avocado oil, sesame oil, evening primrose oil, sunfloweroil, kukui nut oil, jojoba oil, walnut oil, peanut oil, pecan oil,macadamia nut oil, coconut oil, and the like and combinations thereof.

The oils of such embodiments may be supplemented with any of theadditives discussed below, or such oils can be incorporated into thecreams, lotions, salves, liniments, ointments, gels, pastes, tonics,unguents, soaps, shampoos, and lip balms discussed below. Thepreparation of a topical compositions that contain dispersed activeingredients is well understood in the art. Typically, such compositionscan be prepared as sterile compositions either as liquid solutions orsuspensions, aqueous or non-aqueous, however, suspensions in liquidprior to use can also be prepared. The concentration of the cannabinoidor, in certain embodiments, cannabidiol or cannabidiol analogs, incompositions can range from about 0.0002% to about 100% by weight withthe balance of the composition being carriers, excipients, diluents,additives, supplements, such as, vitamin E, and the like andcombinations thereof.

As used herein, the terms “pharmaceutically acceptable”,“physiologically tolerable” and grammatical variations thereof, as theyrefer to compositions, carriers, excipients, diluents, and reagentsrepresent that the materials are capable of administering upon a mammalwithout the production of undesirable physiological effects.

The cannabinoid or, in certain embodiments, cannabidiol or cannabidiolanalogs, can be mixed with excipients that are pharmaceuticallyacceptable and compatible with the active ingredient and in amountssuitable for use in the therapeutic methods described herein. Forexample, the cannabinoid or, in certain embodiments, cannabidiol orcannabidiol analogs, can be dissolved in excipients such as aqueous orsaline based solutions or alcohol-based solutions, containing, forexample, dextrose, glycerol, and the like and combinations thereof. Insome embodiments, the composition can further contain auxiliarysubstances that enhance the effectiveness of the active ingredient suchas wetting or emulsifying agents, pH buffering agents, and the like.These compositions can be administered directly or the compositions canbe used as constituent of therapeutic or cosmetic formulation, such asan emulsion, lotion, spray, ointment, cream, foam, mask, soap, and thelike. The cannabinoid or, in certain embodiments, cannabidiol orcannabidiol analogs, compositions can make up to about 80% of thetherapeutic or cosmetic formulations, and in some embodiments, thecannabinoid or, in certain embodiments, cannabidiol or cannabidiolanalogs, can make up about 0.01% to about 75%, about 0.1% to about 50%,about 0.5% to about 25%, or any range or individual concentrationencompassed by these ranges. For example, an eye cream can contain about0.1% to about 10% cannabinoid or, in certain embodiments, cannabidiol orcannabidiol analogs, in a carrier or excipient, and a facial cream cancontain about 0.01% to about 20% of cannabinoid or, in certainembodiments, cannabidiol or cannabidiol analogs, in a carrier orexcipient. In further embodiments, the cannabinoid or, in certainembodiments, cannabidiol or cannabidiol analogs, in topical formulationscan make up about 10 ug/ml to about 10 mg/ml, or about 1 ug/ml to about10 mg/ml, about 0.1 ug/ml to about 8 mg/ml, about 1 mg/ml to about 5mg/ml, or any range or individual concentration encompassed by theseranges.

A topical composition of invention can include pharmaceuticallyacceptable salts of the cannabinoid or, in certain embodiments,cannabidiol or cannabidiol analogs. Pharmaceutically acceptable saltsinclude the acid addition salts that are formed with inorganic acidssuch as, for example, hydrochloric or phosphoric acids, or such organicacids as acetic, tartaric, mandelic and the like. Salts derived frominorganic bases include, for example, sodium, potassium, ammonium,calcium or ferric hydroxides, and such organic bases as isopropylamine,trimethylamine, ethylamino ethanol, histidine, procaine, and the like.

Physiologically tolerable carriers and excipients are well known in theart. Examples of liquid carriers include sterile aqueous solutions thatcontain no materials in addition to the active ingredients and water, orwater and a buffer such as, for example, sodium phosphate atphysiological pH value, physiological saline, such as phosphate-bufferedsaline and Tris-HCl buffer, and the like and combinations thereof.Aqueous solutions can contain more than one buffer salt, as well assalts such as sodium and potassium chlorides, dextrose, propyleneglycol, polyethylene glycol and other solutes.

The compositions of cannabinoid or, in certain embodiments, cannabidiolor cannabidiol analogs, can be formulated into gels, creams, lotions, orointments. Gels are semi-solid dispersion of liquid or oil particles ina semi-solid medium and may include, for example, petroleum jelly andcoco butter. In these mixtures, the cannabinoid, cannabidiol, orcannabidiol analogs may be in the form of a suspension or form a gelwith the excipient and can be mixed with solids such as starches andmethyl cellulose. Creams refer to semi-solid emulsions of oil and waterin approximately equal proportions. They are divided into two types:oil-in-water (O/W) creams, composed of small droplets of oil dispersedin a continuous phase; and water-in-oil (W/O) creams, composed of smalldroplets of water dispersed in a continuous oily phase. Creams canprovide a barrier to protect the skin. Lotions are low- tomedium-viscosity topical preparation. Most lotions are oil-in-wateremulsions containing an emulsifier such as cetyl alcohol to preventseparation of these two phases, and include, for example, fragrances,glycerol, petroleum jelly, dyes, preservatives, proteins, andstabilizing agents. Ointments are compositions in which oil and waterare provided in a ratio of from 7:1 to 2:1, from 5:1 to 3:1, or 4:1.Ointments are generally formulated using oils, waxes, water, alcohols,petroleum products, water, and other agents to prepare formulations withvarious viscosities and solvent properties. Commonly used ointmentformulations include oleaginous base (White Ointment), absorption base,W/O emulsion base (Cold Cream type base), O/W emulsion base (HydrophilicOintment), water soluble base, in addition to others. These preparationsare used to dissolve or suspend substances or products with medicinal orcosmetic value.

Liquid compositions can also contain liquid phases in addition to and tothe exclusion of water. Exemplary of such additional liquid phases areglycerin, vegetable oils such as cottonseed oil, olive oil, grapeseedoil, tea tree oil, almond oil, avocado oil, sesame oil, evening primroseoil, sunflower oil, kukui nut oil, jojoba oil, walnut oil, peanut oil,pecan oil, macadamia nut oil, coconut oil, and the like and combinationsthereof, organic esters such as ethyl oleate, and water-oil emulsions.

In certain embodiments, formulations containing cannabinoid,cannabidiol, or cannabidiol analogs compositions of the invention cancontain chemical preservatives, such as cetylpyridinium chloride,K-Sorbate, Na-Benzoate, various parabens, other chemical preservatives,and combinations thereof. Other suitable additives include sodiumcompounds and copper-based compounds. In particular, sodium has beenlinked to stimulate elastogenesis.

Cosmetic formulations including lotions, creams, soaps, shampoos, lipbalms may be designed for moisturizing, anti-aging, or anti-wrinkle, ortreating acne, rough skin, dandruff, eczema, and the like as well aslightening or whitening skin.

In some embodiments, topical formulations may further includehydrocortisone or any steroid within Groups I to VII in the USclassification system. Group I steroids include, but are not limited to,clobetasol propionate, betamethasone dipropionate, halobetasol, anddiflorasone diacetate. Group II steroids include, but are not limitedto, fluocinonide, halcinonide, amcinonide, and desoximetasone. Group IIIsteroids include, but are not limited to, triamcinolone acetonide,mometasone furoate, fluticasone propionate, betamethasone dipropionate,and halometasone. Group IV steroids include, but are not limited to,fluocinolone acetonide, hydrocortisone valerate, hydrocortisonebutyrate, flurandrenolide, triamcinolone acetonide, and mometasonefuroate. Group V steroids include, but are not limited to, fluticasonepropionate, desonide, fluocinolone acetonide, and hydrocortisonevalerate. Group VI steroids include, but are not limited to,alclometasone dipropionate, triamcinolone acetonide, fluocinoloneacetonide, and desonide. Group VII steroids include, but are not limitedto, hydrocortisone (2.5%) and hydrocortisone (1%). The amount ofhydrocortisone or steroid within Groups I to VII in the topicalformulation is not particularly limited, so long as it is atherapeutically effective amount. An amount may be from about 0.01% toabout 5%, relative to the total amount of the topical formulation, orabout 0.1% to about 1%, relative to the total amount of the topicalformulation.

In some embodiments, topical formulations may further include anantibiotic compound. The antibiotic compound is not particularlylimited, and may be at least one member selected from the groupconsisting of ampicillin, bacampicillin, carbenicillin indanyl,mezlocillin, piperacillin, ticarcillin, amoxicillin-clavulanic acid,ampicillin-sulbactam, benzylpenicillin, cloxacillin, dicloxacillin,methicillin, oxacillin, penicillin G, penicillin V, piperacillintazobactam, ticarcillin clavulanic acid, nafcillin, procaine penicillin,cefadroxil, cefazolin, cephalexin, cephalothin, cephapirin, cephradine,cefaclor, cefamandol, cefonicid, cefotetan, cefoxitin, cefprozil,ceftmetazole, cefuroxime, loracarbef cefdinir, ceftibuten, cefoperazone,cefixime, cefotaxime, cefpodoxime proxetil, ceftazidime, ceftizoxime,ceftriaxone, cefepime, azithromycin, clarithromycin, clindamycin,dirithromycin, erythromycin, lincomycin, troleandomycin, cinoxacin,ciprofloxacin, enoxacin, gatifloxacin, grepafloxacin, levofloxacin,lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin,sparfloxacin, trovafloxacin, oxolinic acid, gemifloxacin, perfloxacin,imipenem-cilastatin, meropenem, and aztreonam. The amount of theantibiotic compound in the topical formulation is not particularlylimited, so long as it is a therapeutically effective amount. An amountis from about 0.01% to about 5%, relative to the total amount of thetopical formulation, more preferably from about 0.1% to about 1%,relative to the total amount of the topical formulation.

In some embodiments, topical formulations may further include anantiseptic compound. The antiseptic compound is not particularlylimited, and may be at least one member selected from the groupconsisting of iodine, manuka honey, octenidine dihydrochloride, phenol,polyhexanide, sodium chloride, sodium hypochlorite, calciumhypochlorite, sodium bicarbonate, methyl paraben, and sodiumdehydroacetate. The amount of the antiseptic compound in the topicalformulation is not particularly limited, so long as it is atherapeutically effective amount. An amount may be from 0.01% to 5%,relative to the total amount of the topical formulation, more preferablyfrom 0.1% to 1%, relative to the total amount of the topicalformulation.

In some embodiments, topical formulations may further include anantifungal agent. The antifungal agent is not particularly limited, andmay be at least one member selected from the group consisting ofamphotericin B, candicidin, filipin, hamycin, natamycin, nystatin,rimocidin, bifonazole, butoconazole, clotrimazole, econazole,fenticonazole, isoconazole, ketoconazole, luliconazole, miconazole,omoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole,albaconazole, fluconazole, isavuconazole, itraconazole, posaconazole,ravuconazole, terconazole, voriconazole, abafungin, amorolfin,butenafine, naftifine, terbinafine, anidulafungin, caspofungin,micafungin, benzoic acid, ciclopirox, flucytosine, griseofulvin,haloprogin, tolnaftate, undecylenic acid, crystal violet, and balsam ofPeru. The amount of the antifungal agent in the topical formulation isnot particularly limited, so long as it is a therapeutically effectiveamount. An amount may be from about 0.01% to about 5%, relative to thetotal amount of the topical formulation, more preferably from about 0.1%to about 1%, relative to the total amount of the topical formulation.

In some embodiments, the topical formulation may further include ananti-acne compound. The anti-acne agent is not particularly limited, andmay be at least one member selected from the group consisting ofsalicylic acid and benzoyl peroxide. The amount of the anti-acnecompound in the topical formulation is not particularly limited, so longas it is a therapeutically effective amount. An amount of from about0.01% to about 5%, relative to the total amount of the topicalformulation, or about 0.1% to about 1%, relative to the total amount ofthe topical formulation.

In some embodiments, topical formulations may include a humectant, whichcan be referred to as a soothing, smoothing, moisturizing or protectiveagent. The humectant is not particularly limited, and may be at leastone member selected from the group consisting of calamine,dodecylsulphate, sodium lauryl sulphate (SLS), a polyoxyethylene esterof polysorbitan, such as monooleate, monolaurate, monopalmitate,monostearate esters, esters of sorbitan, the polyoxyethylenes ethers,the sodium dioctylsulphosuccinate (DOSS), lecithin, and sodium docusate.Sodium lauryl sulphate and calamine are the most preferred humectants.The amount of the humectant in the topical formulation is notparticularly limited, so long as it is a therapeutically effectiveamount. An amount may be from about 0.01% to about 5%, relative to thetotal amount of the topical formulation, more preferably about 0.1% toabout 1%, relative to the total amount of the topical formulation.

In some embodiments, topical formulations may contain a UV-absorbingcompound, which can be referred to as a sunscreen agent. TheUV-absorbing compound is not particularly limited, and may be at leastone member selected from the group consisting of glyceryl PABA, padimate0, roxadimate, dioxybenzone, oxybenzone, sulisonbenzone, octocrylene,octyl methoxycinnamate, ethoxyethyl p-methoxycinnamate, homomenthylsalicylate, ethylhexyl salicylate, trolamine salicylate, avobenzone,ecamsule, ensulizole, bemotrizinol, and bisoctrizole. The amount of theUV-absorbing compound in the topical formulation is not particularlylimited, so long as it is a therapeutically effective amount. An amountmay be from about 0.01% to about 5%, relative to the total amount of thetopical formulation or about 0.1% to about 1%, relative to the totalamount of the topical formulation.

In some embodiments, topical formulations may include an analgesicagent. The analgesic agent is not particularly limited, and ispreferably at least one member selected from the group consisting ofmethyl salicylate, codeine, morphine, methadone, pethidine,buprenorphine, hydromorphine, levorphanol, oxycodone, fentanyl, and anon-steroidal anti-inflammatory drug (NSAID). The amount of theanalgesic agent in the topical formulation is not particularly limited,so long as it is a therapeutically effective amount. An amount may befrom about 0.01% to about 5%, relative to the total amount of thetopical formulation, or about 0.1% to about 1%, relative to the totalamount of the topical formulation.

An “effective amount” is a predetermined amount of cannabinoid,cannabidiol, or cannabidiol analogs calculated to achieve the desiredeffect, for example, to effectively promote lighten the color of skin,reduce production of melanin, diminish the amount of melanin in skin,reduce visible redness, or combinations thereof. Thus, the dosage rangesfor the administering of cannabinoid, cannabidiol, or cannabidiolanalogs are those large enough to produce the desired effect withoutcausing adverse side effects. Generally, the dosage will vary with theage, condition, and sex of the patient, and can be determined by one ofskill in the art. The dosage can be adjusted in the event of anycomplication.

The compositions and formulations discussed above, can be administeredin a manner compatible with the dosage formulation, and in atherapeutically effective amount. Suitable regimes for administrationare also variable, but are typified by an initial administrationfollowed by repeated doses at one or more time intervals by a subsequentadministration. Where a single composition is not available for atreatment, or where such a composition is not desirable, administrationof composition may also include the application of several differentcompositions sequentially to achieve a desired effect.

“Providing” when used in conjunction with a therapeutic means toadminister a therapeutic directly onto a target tissue or to administera therapeutic to a patient whereby the therapeutic positively impactsthe tissue to which it is targeted. Thus, as used herein, the term“providing”, when used in conjunction with cannabinoid or, in certainembodiments, cannabidiol or cannabidiol analogs, can include, but is notlimited to, providing a cannabinoid or, in certain embodiments,cannabidiol or cannabidiol analogs, onto the target tissue. “Providing”a composition may be accomplished by topical administration, or byeither method in combination with other known techniques. Suchcombination techniques include heating, radiation and ultrasound.

Heating skin on a patient may open pores, activate the variousmechanisms of a cell, and increase diffusion into said tissue and cells.Thus, heating in connection with providing a therapeutic composition isan aspect of the invention.

Embodiments can further include local administration of compositions orformulations containing cannabinoid, cannabidiol, or cannabidiol analogsto skin of a mammal. Local administration is typically carried out bytopical administration of a liquid, gel, cream, ointment, or lotioncontaining the compositions of various embodiments.

In some embodiments, the formulations can be in the form of a soap,which are formulations that comprise a salt of a fatty acid. Soaps aremainly used as surfactants for washing, bathing, and cleaning, but theyare also used in textile spinning and are important components oflubricants. Soaps for cleansing are usually obtained by treatingvegetable or animal oils and fats with a strongly alkaline solution.Fats and oils are composed of triglycerides; three molecules of fattyacids are attached to a single molecule of glycerol. The alkalinesolution, which is often called lye (although the term “ye soap” refersalmost exclusively to soaps made with sodium hydroxide), is believed topromote a chemical reaction known as saponification. In saponification,the fats are first hydrolyzed into free fatty acids, which then combinewith the alkali to form crude soap. Glycerol (glycerine) is usuallyliberated and is either left in or washed out and recovered as a usefulbyproduct, depending on the process employed.

In some embodiments, the topical formulations can be in the form of ashampoo, which is a hair care product used for the removal of oils,dirt, skin particles, dandruff, environmental pollutants, and othercontaminant particles that gradually build up in hair.

Additional embodiments are directed to methods for making the topicalformulations including cannabinoid or, in certain embodiments,cannabidiol or cannabidiol analogs. Such methods may include dispersingthe cannabinoid, cannabidiol, or cannabidiol analogs into mineral oil orsilicone oil to obtain an oil phase; dispersing an emulsifier, athickener; and a stabilizer into water in a separate vessel to obtain anaqueous phase; and blending the oil phase and the aqueous phase to forman emulsion. In various embodiments, such methods may include dispersingcannabinoid, cannabidiol, or cannabidiol analogs into the aqueous phaseor the emulsion, rather than into the oil phase. In some embodiments,the method further include the step of heating during at the steps ofobtaining an oil phase or dispersing an emulsifier, a thickener; and astabilizer into water in a separate vessel to obtain an aqueous phase.Temperatures of this heating are not particularly limited, so long asthe oil phase and the aqueous phase result from the dispersing.

In some embodiments, methods for making the topical formulations caninclude mixing an oil phase including cannabinoid, cannabidiol, orcannabidiol analogs and an emulsifier with an aqueous phase to form amixture, and heating said mixture at a temperature of from 45° C. and85° C. to form an aqueous emulsion. Emulsifiers include, but are notlimited to, cetyl alcohol, stearic acid, and a mixture thereof. Thewater phase may further include a stabilizing agent such as VEEGUM® orCARBOPOL®, and further embodiments, include adding one or moreadditives, such as fragrances, glycerol, petroleum jelly, colorants,dyes, preservatives, proteins, and the like. Such methods may producelotions.

In further embodiments, methods for making the topical formulation caninclude combining a surfactant such as, for example, sodium laurylsulfate, sodium laureth sulfate, or combinations thereof with aco-surfactant such as cocamidopropyl betaine, in an aqueous phase andmixing the aqueous phase with an oil phase containing cannabinoid,cannabidiol, or cannabidiol analogs to form a viscous liquid. Methodscan include adding other additives, such as salt (sodium chloride), apreservative, and fragrance, to the aqueous phase.

Further embodiments are directed to methods for whitening or lighteningskin of a subject and/or reducing fine lines and wrinkles, firming andlifting of the skin, promoting collagen production, generally reducingthe signs of aging, and combinations thereof that include applying aneffective amount of a topical formulation containing cannabinoid,cannabidiol, or cannabidiol analogs such as those describe aboveaccording to skin of a subject. Non-limiting examples of targeteddermatological diseases include eczema, psoriasis, sunburn, contactdermatitis, poison ivy and conditions caused by other plant materialscontaining urushiol or related molecules, type 1 and type 2 herpes,insect bites, anal itching, vaginal itching, acne, warts and other acuteand chronic dermatoses afflicting humans, and use as a topical analgesicfor muscle and arthritic pain. Psoriasis is the preferred targeteddermatological disease.

EXAMPLES

Although the present invention has been described in considerable detailwith reference to certain preferred embodiments thereof, other versionsare possible. Therefore, the spirit and scope of the appended claimsshould not be limited to the description and the preferred versionscontained within this specification. Various aspects of the presentinvention will be illustrated with reference to the followingnon-limiting examples.

Example 1

Weighed 1.5 grams of subcritical CO₂ extracted CBDA (40.13 wt. % CBDA)into jar. To this was added 30 grams of Jerkins “Ultra-Healing” dry skincream as a suitable base. This was thoroughly mixed by hand until auniform, light yellow cream (1). A second control sample was prepared ofonly 30 grams Jerkins “Ultra-Healing” dry skin cream (2).

These samples were applied two times daily to left and right handsindependently for 35 days. Control cream (2), 0.5 milliliters wasapplied during the morning and evening every day, thoroughly 1 inchabove the wrist of the left hand and evening every day over the entireback of hand to the fingertips. Lightening cream (1), 0.5 milliliterswas applied during the morning, thoroughly 1 inch above the wrist of theright hand and over the entire back of hand to the fingertips, and.

Noticeable lightening of the right hand began to occur after 2 weeks(about 14 days) of application, and lightening continued for theduration of experiment. The left hand unchanged throughout the treatmentperiod. See FIG. 1A-C. No irritation, rash, redness, itchiness ordiscomfort of any kind was reported during this trial.

1. A method for lightening skin tone, comprising topically administeringa composition containing a cannabinoid, cannabidiol, cannabidiol analog,or combinations thereof.
 2. The method of claim 1, wherein lighteningcomprises lightening color of skin, reducing production of melanin,diminishing the amount of melanin in skin, reducing redness of skin, orcombinations thereof.
 3. The method of claim 1, wherein the compositioncomprises cannabinoids containing about 30 w/v % to about 100 w/v %cannabidiol.
 4. The method of claim 1, wherein the composition comprisesup to about 80 wt. % cannabidiol.
 5. The method of claim 1, wherein thecomposition comprises about 0.1 wt. % to about 50 wt. % cannabidiol. 6.The method of claim 1, wherein the composition comprises about 0.5 wt. %to about 25 wt. % cannabidiol.
 7. The method of claim 1, wherein thecomposition comprises about 10 ug/ml to about 10 mg/ml cannabidiol. 8.The method of claim 1, wherein the composition comprises a about 0.1ug/ml to about 8 mg/ml cannabidiol.
 9. The method of claim 1, whereinthe composition is a semi-solid emulsion of oil and water inapproximately equal proportions.
 10. The method of claim 1, wherein thecomposition is an oil-in-water (O/W) cream or a water-in-oil (W/O)cream.
 11. The method of claim 1, wherein the composition furthercomprises an agent selected from the group consisting of steroids,antibiotics, antiseptics, antifungals, anti-acne compounds, humectants,UV-absorbing compounds, analgesics, and combinations thereof.
 12. Amethod for reducing signs of aging, comprising topically administering acomposition containing a cannabinoid, cannabidiol, cannabidiol analog,or combinations thereof.
 13. The method of claim 12, reducing the signsof aging comprises reducing fine lines, reducing wrinkles, firming skin,lifting skin, and reducing sagging.
 14. The method of claim 12, whereinthe composition comprises cannabinoids containing about 30 w/v % toabout 100 w/v % cannabidiol.
 15. The method of claim 12, wherein thecomposition comprises up to about 80 wt. % cannabidiol.
 16. The methodof claim 12, wherein the composition comprises about 0.1 wt. % to about50 wt. % cannabidiol.
 17. The method of claim 12, wherein thecomposition comprises a about 0.1 ug/ml to about 8 mg/ml cannabidiol.18. The method of claim 12, wherein the composition is a semi-solidemulsion of oil and water in approximately equal proportions.
 19. Themethod of claim 12, wherein the composition is an oil-in-water (O/W)cream or a water-in-oil (W/O) cream.
 20. The method of claim 12, whereinthe composition further comprises an agent selected from the groupconsisting of steroids, antibiotics, antiseptics, antifungals, anti-acnecompounds, humectants, UV-absorbing compounds, analgesics, andcombinations thereof.